Core Cannabis Course: CBDA

Welcome to homework assignment CCC 1.2 of the Core Cannabis Course from Higher Learning LV. This assignment teaches students about the cannabinoid CBDA, the acidic precursor to the major neutral cannabinoid CBD (one of the two most commercially popular cannabinoids, along with delta-9 THC). Peer-reviewed research has shown that CBDA possesses anticonvulsive, antidepressant, and anti-inflammatory properties.

When you complete this assignment, simply click the link at the bottom of the article to return to the master page for this course.

Cannabidiolic acid (CBDA) is the acidic precursor to cannabidiol, or CBD. CBDA is one of the most common cannabinoids produced by cannabis and hemp. It is derived from the "mother of all cannabinoids," cannabigerolic acid (CBGA), which also produces the important cannabinoids tetrahydrocannabinolic acid (THCA) and cannabichromenic acid (CBCA). All of these cannabinoids are covered in this course and feature dedicated homework assignments, each with multiple research summaries.

CBDA molecular structure

Although not psychoactive, research has revealed that CBDA delivers a wide range of potential medicinal benefits, including anti-inflammatory and anti-seizure properties. If decarboxylated with heat or flame, CBDA morphs into CBD. This occurs when cannabis consumers vaporize or smoke the loose-leaf flowers of the plant.

CBDA biosynthetic pathway

The primary potential medicinal benefits of CBDA are found in its anti-inflammatory and anticonvulsant properties. However, it has also demonstrated the ability to fight pain.

Like other cannabinoids, CBDA has displayed anti-nausea properties, making it of potential benefit to those undergoing chemotherapy, including patients with HIV/AIDS, cancer, and Crohn's disease. In addition, this cannabinoids has exhibited potential benefits for obesity.

A 2022 study entitled "The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity" that was published in the International Journal of Molecular Sciences explored the potential ability of a stabilized form of CBDA to decrease appetite and play a therapeutic role in the treatment of obesity.

The rodent study reported that while the anti-obesity properties of CBD have been "reasonably identified," knowledge of the pharmacological characteristics of CBDA are more limited and this is largely due to its chemical instability. To stabilize the cannabinoid, the scientists synthesized a new derivative, CBDA-O-methyl ester (EPM301). The goal was to create a stable version of CBDA to study its role in "appetite reduction, weight loss, and metabolic improvements."

Molecular structures of CBD (A), CBDA (B), and CBDA-O-methyl ester (EPM301) (C)

The scientists fed male mice the CBDA derivative for 28 days. They found that this version of CBA reduced body weight and fast mass and that it achieved this "without any significant effect on lean mass."

Perhaps most important, the study found that EPM301, the CBDA isomer, completely restored "the voluntary wheel running ability of the mice." The scientists theorized that this may suggest that EPM301 and CBDA "may reduce obesity-induced depression symptoms."

The study found that EPM301, the CBDA isomer, completely restored "the voluntary wheel running ability of the mice."

The researchers concluded that the EPM301 derivative of CBDA "may share mutual mechanisms with CBD" and that this could help explain some of its biochemical properties with respect to the treatment of obesity. The study summarized that EPM301 "displayed an impressive ability to ameliorate obesity and its metabolic abnormalities in...animal models and cells."

It concluded that EPM301 prevented the rodents from gaining weight and fat and that its results support further research on CBDA derivatives such as EPM301 for clinical evaluation in human trials for obesity, particularly for those who "currently have no effective therapy available."

View the original study.

A 2020 study entitled "Evaluation of Repeated or Acute Treatment with Cannabidiol (CBD), Cannabidiolic Acid (CBDA), or CBDA Methyl Ester (HU-580) on Nausea and/or Vomiting in Rats and Shrews" that was published in the journal Psychopharmacology explored the ability of CBD and CBDA to manage nausea and tested "if their effectiveness is maintained when injected subcutaneously and when repeatedly administered."

The study gave the test subjects "both acute and repeated (7 day) subcutaneous administrations of CBD (5 mg/kg), CBDA (1 μg/kg), and HU-580 (1 μg/kg)." It found that all three cannabinoids provided anti-nausea powers. To test if this mechanism would diminish over time and with repeated treatments, the researchers administered CBD and CBDA over a four-week period. They found that the anti-nausea effectiveness of these cannabinoids was maintained.

The study's authors concluded that CBD and CBDA, when administered repeatedly over a seven-day period, "did not lose efficacy in reducing nausea."

The study's authors concluded that CBD and CBDA, when administered repeatedly over a seven-day period, "did not lose efficacy in reducing nausea." When treated over a four-week period, the cannabinoids continued to maintain their anti-nausea properties. "Repeated CBD also reduced vomiting in shrews," reported the scientists. As far as gender differences in study participants, the research reported that the anti-nausea effects "were similar in male and female rats."

The study surmised that the cannabinoids CBD and CBDA "may be useful anti-nausea and anti-emetic treatments for chronic conditions" and that they may lack the development of tolerance, unlike some conventional treatments.

View the original study.

A 2018 study entitled "Elucidation of Structure-function Relationship of THCA and CBDA Synthase from Cannabis sativa L." that was published in the Journal of Biotechnology explored a variety of acidic precursor cannabinoids, including CBCA, CBDA, CBGA, and THCA. The research also investigated the precursors to the precursors, the acid synthase molecules CBDAS and THCAS (eventually resulting in CBD and THC, respectively).

The study reported that cannabinoids are "predominantly found in the oil compartments of trichomes of the plant Cannabis sativa L." and that more than 100 have been discovered—with discovery defined as having been chemically isolated—as of 2017.

"Many of these phytocannabinoids are derived from the three most abundant acidic cannabinoids: Δ9-tetrahydrocannabinolic acid-A (THCA), cannabichromenic acid (CBCA), and cannabidiolic acid (CBDA)."

"Many of these phytocannabinoids are derived from the three major, most abundant acidic cannabinoids—namely Δ9-tetrahydrocannabinolic acid-A (THCA), cannabichromenic acid (CBCA), and cannabidiolic acid (CBDA)—by non-enzymatic transformations and degradation reactions upon heat and light exposure, as well as auto-oxidation," reported the study.

Students should note that the scientists have taught a valuable element of cannabinoid science. The two primary mechanisms that result in the transmogrification of acidic precursor cannabinoids into their neutral isomers (such as CBDA > CBD) are 1) enzymatic catalyst molecules and 2) environmental stressors. Among the environmental elements are exposure to heat, UV light, and oxygen.

The scientists noted that delta-9 THC is commonly employed in the treatment of "chemotherapy-associated nausea and vomiting, AIDS-related loss of appetite, and pain and muscle spasms in multiple sclerosis," roles for which it has been approved (under rigorous regulatory scrutiny) by the U.S. federal government via the FDA. They reported that THCA, which is not psychoactive and about which students will learn later in this course, has shown positive efficacy in terms of being "immunomodulatory, anti-inflammatory, and neuroprotective."

The study reported that, while delta-9 THC has been approved by the FDA for certain applications due to its active pharmaceutical properties, the cannabinoids CBC and CBD have not. However, both of these cannabinoids are being investigated for potential efficacy for a range of disease states, including Alzheimer's disease, Parkinson's disease, cancer, and—in the case of CBD—epilepsy. CBC is being analyzed for a range of chemical characteristics, including "anti-inflammatory, anti-fungal, antibiotic, and analgesic [pain killing] effects."

Interestingly, the CBDA synthase was considered to be the "ancestral synthase from which the THCA synthase [THCAS] evolved."

View the original study.

Juicing the leaves of mature cannabis plants is one of the best ways to get CBDA into your body. However, many patients and consumers do not have access to the raw leaves of the plant. Such consumers can create infused food with loose-leaf hemp flower that they purposefully do not decarboxylate.

Some companies sell products like tinctures, capsules, gummies, and topicals that are formulated with CBDA.